Biomarker analysis of the phase II JO25567 study comparing erlotinib with or without bevacizumab in first-line advanced EGFR+non-small-cell lung cancer.

Background: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), such as erlotinib, are standard-of-care for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC), but most patients progress within 1 year. Previously, we demonstrated that erlotinib plus bevacizumab (EB) improved progression-free survival (PFS) in patients with EGFR-positive non-squamous NSCLC in the randomized JO25567 study. To understand this effect, we conducted comprehensive exploratory biomarker analyses. Methods: Using blood and tissue specimens from patients enrolled in the JO25567 study, angiogenesis-related serum factors, plasma vascular endothelial growth factor-A (pVEGFA), angiogenesis-related gene polymorphisms, and messenger RNAs (mRNAs) in tumor tissue were analyzed. Interactions between potential predictors and treatment effect on PFS were analyzed in a Cox model. Continuous variable predictors were evaluated by multivariate fractional polynomial interaction methodology and subpopulation treatment effect pattern plotting (STEPP). Results: Overall, 152 patients treated with EB or erlotinib alone (E) were included in the analysis. Among 26 factors analyzed in 134 baseline serum samples, high follistatin and low leptin were identified as potential biomarkers for worse and better outcomes with EB, with interaction P values of 0.0168 and 0.0049, respectively. Serum concentrations of 12 angiogenic factors were significantly higher in patients with high follistatin. Low pVEGFA levels related to better outcomes with EB, interaction P=0.033. VEGF-A165a was the only predictive tissue mRNA, showing a similar trend to pVEGFA. No valid results were obtained in 13 polymorphisms of eight genes. Conclusions: EB treatment showed better treatment outcomes in patients with low pVEGFA and serum leptin, and limited efficacy in patients with high serum follistatin.

Prospective screening for myocarditis in cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) improve clinical outcomes in various cancers, but sometimes induce autoimmune adverse effects, including myocarditis, which is the most serious complication. There are many reports on ICI-induced myocarditis; however, only a few prospective surveillance reports exist. Therefore, we developed a prospective screening protocol and performed monitoring clinically suspected myocarditis in every patient treated with ICIs. METHODS: We prospectively enrolled 126 consecutive patients treated with ICIs in this cohort. Outcomes of patients were determined and analyzed between April 2017 and May 2020. We evaluated vital signs, biomarkers, electrocardiograms, chest radiographs, and echocardiographs before and at 7 ±â€¯3, 14 ±â€¯3, 21 ±â€¯3, and 60 ±â€¯7 days after ICI initiation. RESULTS: Eighteen (14.3 %) presented troponin I elevation and 13 of them presented signs of clinically suspected myocarditis (10.3 %). Among the 13 patients, ICI was discontinued in four cases (3.2 %) without fatal events. Myocarditis appeared at an early stage of ICI treatment, regardless of severity (median, 44 days). CONCLUSIONS: We observed the frequency of patients with myocarditis or myocardial damage through a prospective screening program in the real world. Although the frequency was higher than expected, most cases were mild and ICI treatment could be continued under careful observation.

Multicenter study of zoledronic acid administration in non-small-cell lung cancer patients with bone metastasis: Thoracic Oncology Research Group (TORG) 1017.

Skeletal-related events (SREs) may occur at the time of first diagnosis in 20-30% of lung cancer patients with bone metastases. Several clinical trials have shown that zoledronic acid (ZA) is effective for decreasing SREs. The main objective of the present study was to discuss clinical data of ZA and compare the frequency of SREs with previous reports. All patients with non-small-cell lung cancer (NSCLC) with metastatic bone disease who were administered ZA at least twice between January 2008 and December 2009 were eligible for inclusion in the study. In total, 198 consecutive patients were identified. The median duration of ZA administration was 106 days [95% confidence interval (CI), 92-133 days], and the median number of ZA administrations was 4 (range, 2-41). The median time to first SRE in patients who experienced SRE following ZA treatment was 202 days (95% CI, 156-264 days). Among the 78 patients who had already experienced SRE prior to ZA treatment, 35 (45%) experienced SRE subsequently after starting ZA treatment. On the other hand, among the 120 patients without a history of SRE before starting ZA treatment, 42 (35%) experienced SRE after the start of ZA administration (P=0.16). No osteonecrosis of the jaw (ONJ) was reported in any of the patients. The present study revealed that ZA had a certain level of efficacy regardless of the presence or absence of prior SREs. However, the duration of ZA therapy was short in this study; further accumulation of data on the long-term prognosis and incidence rates of ONJ and other late complications of ZA therapy seems to be particularly important.

Long-term results of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced non-small-cell lung cancer.

PURPOSE: The purpose of this phase I/II study was to evaluate the feasibility and efficacy of S-1 plus cisplatin at the recommended schedule with concurrent thoracic radiotherapy for locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Eligible patients with LA-NSCLC were treated with cisplatin intravenously at a dose of 60 mg/m2 on day 8 plus oral S-1 at a dosage of 40 mg/m2 twice per day for two different treatment schedules for up to 4 cycles. Patients also concurrently received 60 Gy of thoracic radiation in 30 fractions. The primary endpoint of the phase II study was the proportion of patients who survived for more than 2 years. RESULTS: Between August 2005 and October 2010, a total of 45 patients were enrolled in this phase I/II study; their long-term survival was then followed for a median period of 5.8 years. Nineteen of the 39 patients in the phase II study survived for more than 2 years and met the primary endpoint of the study. The median overall survival period was 24.9 months [95% confidence interval (CI) 17.4-74.5 months], and the 2- and 5-year overall survival rates were 51.0 and 43.0%, respectively. The response rate was 85%, and the median progression-free survival period was 13.8 months (95% CI 9.5-27.1 months). Hematological toxicity was mild. Grade 3 febrile neutropenia and pneumonitis was observed in 5 and 5%, respectively. CONCLUSION: Our study indicated that S-1 plus cisplatin with concurrent thoracic radiotherapy yielded encouraging survival outcomes and an acceptable safety profile for LA-NSCLC.

A prospective cohort study of patients with non-squamous non-small cell lung cancer treated with bevacizumab.

First-line chemotherapy regimens that include bevacizumab (Bev) have been hypothesized to improve outcomes in patients with advanced non-squamous non-small cell lung cancer (non-sq NSCLC). Although approved to treat NSCLC in 2009, insufficient data exist on the clinical uses of Bev in Japan. The present study prospectively evaluated the efficacy and safety of Bev-containing combination chemotherapy. Eligible patients exhibited histologically or cytologically documented advanced or recurrent non-sq NSCLC. Patients were administered 15 mg/kg Bev with standard chemotherapy followed by maintenance Bev. The primary endpoints were progression-free survival (PFS) and safety. A total of 102 patients with non-sq NSCLC were enrolled, 44.1% of whose tumor carried epidermal growth factor receptor (EGFR) mutations. The overall response rate to the intervention was 44.1%, and the median PFS was 8.3 months [95% confidence interval (CI)=6.4-10.2 months]. The median overall survival was 26.3 months (95% CI=22.2-30.4 months). The incidence of Bev-associated severe adverse events was similar to those in previous trials, excluding a grade 3-4 hypertension rate of 30.4% in the present study. Multivariate analysis revealed that a higher TNM classification of malignant tumor staging-T factor, adjusted hazard ratio (HR)=1.33 (95% CI=1.10-1.61), and poor performance status [adjusted HR=1.63 (1.02-2.60)] were associated with significantly shorter PFS, whilst the EGFR exon 19 deletion was significantly associated with prolonged PFS [adjusted HR=0.47 (0.25-0.87)]. Bev-containing chemotherapy was safe and effective for patients with non-sq NSCLC in clinical settings in Japan. The EGFR exon 19 deletion was suggested as a positive predictive factor for the efficacy of Bev-containing chemotherapy.

Nedaplatin plus docetaxel versus cisplatin plus docetaxel for advanced or relapsed squamous cell carcinoma of the lung (WJOG5208L): a randomised, open-label, phase 3 trial.

BACKGROUND: The combination of nedaplatin, a cisplatin derivative, and docetaxel showed promising activity for advanced squamous cell lung carcinoma in a previous phase 1-2 study. We compared nedaplatin plus docetaxel with cisplatin plus docetaxel in patients with previously untreated advanced or relapsed squamous cell lung carcinoma to determine effects on overall survival. METHODS: We did a randomised, open-label, phase 3 study at 53 institutions in Japan. Eligibility criteria included pathologically proven squamous cell lung cancer with stage IIIB/IV or postoperative recurrence, age 20-74 years, Eastern Cooperative Oncology Group performance status of 0-1, no previous chemotherapy or recurrence more than a year after previous adjuvant chemotherapy, and adequate organ function. Patients were randomly assigned (1:1) to 100 mg/m(2) nedaplatin and 60 mg/m(2) docetaxel intravenously, or 80 mg/m(2) cisplatin and 60 mg/m(2) docetaxel, every 3 weeks for four to six cycles (at the treating oncologist's discretion). Randomisation was done centrally at the West Japan Oncology Group data centre via a computer-generated allocation sequence with dynamic minimisation that balanced stage (IIIB/IV or postoperative recurrent), sex, and institution. The primary endpoint was overall survival in the modified intention-to-treat population (ie, all patients who were randomly assigned and met the inclusion criteria). Safety analyses were done in all randomly assigned patients who received at least one dose of the study regimen. This trial is registered with the UMIN Clinical Trials Registry, number UMIN000002015, and is closed to new participants. FINDINGS: Between July 6, 2009, and July 26, 2012, 355 patients were randomly assigned. 349 patients were included in the modified intention-to-treat analysis (177 in the nedaplatin group and 172 in the cisplatin group). Overall survival was significantly longer in the nedaplatin group (median 13·6 months, 95% CI 11·6-15·6) than in the cisplatin group (11·4 months,10·2-12·2; hazard ratio 0·81, 95% CI 0·65-1·02; p=0·037, one-sided stratified log-rank test). Grade 3 or worse nausea (seven of 177 patients in the nedaplatin group and 25 of 175 in the cisplatin group), fatigue (six vs 20), hyponatraemia (24 vs 53), and hypokalaemia (four vs 15) were more frequent in the cisplatin group than in the nedaplatin group, whereas grade 3 or worse leucopenia (98 vs 77), neutropenia (146 vs 123), and thrombocytopenia (16 vs none) were more frequent in the nedaplatin group than in the cisplatin group. Treatment-related deaths occurred in four and three patients in nedaplatin and cisplatin groups, respectively. INTERPRETATION: Overall survival was significantly longer with nedaplatin plus docetaxel than with cisplatin plus docetaxel, and the regimens had different safety profiles. Nedaplatin plus docetaxel could be a new treatment option for advanced or relapsed squamous cell lung cancer. FUNDING: West Japan Oncology Group and Sanofi.

Prognostic Factors for Survival After Recurrence in Patients With Completely Resected Lung Adenocarcinoma: Important Roles of Epidermal Growth Factor Receptor Mutation Status and the Current Staging System.

UNLABELLED: Epidermal growth factor receptor (EGFR) status and pathological stage (p-stage) were shown to be essential prognostic factors for estimating survival after recurrence of lung adenocarcinoma. In patients with EGFR mutations, those with early p-stage tumors showed better survival after disease recurrence than those with advanced p-stage tumors. The EGFR mutation status and p-stage could also prompt the design of clinical trials on adjuvant therapy for patients after complete surgical resection. BACKGROUND: The current staging system and epidermal growth factor receptor (EGFR) mutation status are key factors for predicting survival. However, the significance of these factors as predictors of survival after disease recurrence (PRS) has not been sufficiently elucidated. The objective of this study was to investigate the clinicopathological factors, particularly the EGFR mutation status and pathological stage (p-stage), which affect PRS in patients with completely resected lung adenocarcinoma. PATIENTS AND METHODS: We retrospectively reviewed the data of 198 consecutive lung adenocarcinoma patients with disease recurrence who previously underwent complete surgical resection in our hospital. RESULTS: Of the 198 patients, 117 were examined for EGFR mutations (mutants). Mutants were detected in 57 patients (28.7%). The patients with mutants had a significantly better 3-year PRS (3y-PRS) rate (68.6%) than those with an EGFR wild type (WT) status (51.7%) or an unknown (UN) status (27.0%). The 3y-PRS rates for p-stage I to II (p-I-II) and p-stage III (p-III) were 52.5% and 29.3%, respectively. Multivariate survival analysis showed that the EGFR mutation status and p-stage had significant associations with favorable PRS. The 3y-PRS rate for mutants/p-I-II (81.4%) was significantly better than that for mutants/p-III (48.0%). Conversely, there was no significant difference between mutants/p-III and WT/UN/p-I-II (3y-PRS: 40.7%) or between mutants/p-III and WT/UN/p-III (3y-PRS: 24.4%). CONCLUSION: EGFR status and p-stage were shown to be essential prognostic factors for estimating PRS. In patients with mutants, those with early p-stage tumors showed better PRS than those with advanced p-stage tumors.

Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study.

BACKGROUND: With use of EGFR tyrosine-kinase inhibitor monotherapy for patients with activating EGFR mutation-positive non-small-cell lung cancer (NSCLC), median progression-free survival has been extended to about 12 months. Nevertheless, new strategies are needed to further extend progression-free survival and overall survival with acceptable toxicity and tolerability for this population. We aimed to compare the efficacy and safety of the combination of erlotinib and bevacizumab compared with erlotinib alone in patients with non-squamous NSCLC with activating EGFR mutation-positive disease. METHODS: In this open-label, randomised, multicentre, phase 2 study, patients from 30 centres across Japan with stage IIIB/IV or recurrent non-squamous NSCLC with activating EGFR mutations, Eastern Cooperative Oncology Group performance status 0 or 1, and no previous chemotherapy for advanced disease received erlotinib 150 mg/day plus bevacizumab 15 mg/kg every 3 weeks or erlotinib 150 mg/day monotherapy as a first-line therapy until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, as determined by an independent review committee. Randomisation was done with a dynamic allocation method, and the analysis used a modified intention-to-treat approach, including all patients who received at least one dose of study treatment and had tumour assessment at least once after randomisation. This study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-111390. FINDINGS: Between Feb 21, 2011, and March 5, 2012, 154 patients were enrolled. 77 were randomly assigned to receive erlotinib and bevacizumab and 77 to erlotinib alone, of whom 75 patients in the erlotinib plus bevacizumab group and 77 in the erlotinib alone group were included in the efficacy analyses. Median progression-free survival was 16·0 months (95% CI 13·9-18·1) with erlotinib plus bevacizumab and 9·7 months (5·7-11·1) with erlotinib alone (hazard ratio 0·54, 95% CI 0·36-0·79; log-rank test p=0·0015). The most common grade 3 or worse adverse events were rash (19 [25%] patients in the erlotinib plus bevacizumab group vs 15 [19%] patients in the erlotinib alone group), hypertension (45 [60%] vs eight [10%]), and proteinuria (six [8%] vs none). Serious adverse events occurred at a similar frequency in both groups (18 [24%] patients in the erlotinib plus bevacizumab group and 19 [25%] patients in the erlotinib alone group). INTERPRETATION: Erlotinib plus bevacizumab combination could be a new first-line regimen in EGFR mutation-positive NSCLC. Further investigation of the regimen is warranted. FUNDING: Chugai Pharmaceutical Co Ltd.

Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study.

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.

Histology and smoking status predict survival of patients with advanced non-small-cell lung cancer. Results of West Japan Oncology Group (WJOG) Study 3906L.

INTRODUCTION: Smoking status is one of the prognostic factors in advanced non-small-cell lung cancer (NSCLC). Currently, adenocarcinoma (Ad) histology is considered a predictive factor in advanced NSCLC. We investigated the correlation between histology or smoking status and survival of NSCLC patients receiving chemotherapy. METHODS: We retrospectively reviewed clinical data from stage IIIB or IV NSCLC patients who started first-line chemotherapy at affiliated institutions of West Japan Oncology Group from 2004 to 2005. We also collected information on pack-years of cigarette smoking and years since cessation. Overall survival was compared using log-rank test, and Cox regression analysis was used to identify independent prognostic factors. RESULTS: In total, 2542 consecutive patients were enrolled at 40 institutions. Of those, 71 were excluded because of unknown smoking history. The median overall survival of nonsmoking Ad patients (593 days) was longer than that of smoking Ad, nonsmoking non-Ad, and smoking non-Ad patients (384, 374, and 319 days, respectively; p < 0.001). In Cox regression with sex, age, stage, performance, and treatment as covariates, we found significant interaction (p = 0.039) between histology (Ad/non-Ad) and smoking status (smoker/nonsmoker); smoking conferred a hazard ratio of 1.34 (95% confidence interval, 1.15-1.55) in Ad, but only 0.99 (0.75-1.31) in non-Ad. Higher pack-years and shorter period since cessation were significantly associated with poorer survival in Ad (p < 0.001), but not in non-Ad (p ≥ 0.434). CONCLUSION: Ad histology is associated with better prognosis, and only smoking status had a prognostic impact in Ad.

[Results of questionnaire on decision-making to treat advanced non-small cell lung cancer based on American and European practical guidelines].

During 2009, practical routine guidelines for advanced non-small cell lung cancer used in Europe or USA were updated because the clinical benefits of molecular target agents were confirmed through several pivotal clinical trials. These molecular target agents appeared in guidelines which became available in Japan by the end of 2009. We made a questionnaire for decision-making to treat advanced non-small cell lung cancer based on these practical guidelines. Oncologists of lung cancer working in the Shinjuku area of Tokyo in Japan were eligible. Between March 15th and April 9th in 2010, 28 oncologists from 12 departments in 7 hospitals completed this questionnaire. Most of them made the global standard decision-making according to the new guidelines, including new proposals such as usage of epidermal growth factor receptor-tyrosine kinase inhibitors. There were 3 differences from the guidelines. 1)Platinum doublets were selected even in 2nd- or 3rd-line treatment because of the expected tumor shrinkage. 2)Single cytotoxic agents were selected even for 3rd-line treatment. The tendency of a backward shift in decision-making was observed. 3)There were few selections of regimens including bevacizumab because of medical systems such as DPC(Diagnosis Procedure Combination)that is Japanese DRG(Diagnosis-Related Group)/PPS(Prospective Payment System).

Individualized adjuvant chemotherapy for surgically resected lung cancer and the roles of biomarkers.

Several prospective randomized trials for patients with completely resected stages II and IIIA nonsmall cell lung cancer have confirmed a survival benefit with cisplatin-based adjuvant chemotherapy. The Lung Adjuvant Cisplatin Evaluation, which is based on pooled analyses of five randomized trials, has demonstrated a 4.2% absolute survival benefit at 5 years. The stage is the benchmark standard used to decide the indication for adjuvant chemotherapy; however, it is important to identify and select the patients who would benefit from adjuvant chemotherapy and to choose the optimal regimen for each case. The translational research was performed using specimens obtained in the above adjuvant trials also to obtain information concerning biomarkers and subsets of patients who would benefit from adjuvant chemotherapy. The extent to which individualized treatment of lung cancer can be provided, especially adjuvant chemotherapy, is discussed in this manuscript.

Detection of unsuspected distant metastases and/or regional nodes by FDG-PET [corrected] scan in apparent limited-disease small-cell lung cancer.

We retrospectively investigated the clinical usefulness of fluorodeoxyglucose positron emission tomography (FDG-PET) for evaluation of patients with limited-disease small-cell lung cancer (LD-SCLC) diagnosed by conventional staging procedures. Sixty-three patients received whole body FDG-PET scans after routine initial staging procedures. The findings of FDG-PET scans suggesting extensive-stage disease were confirmed by other imaging tests or by the patient's clinical course. FDG-PET scan findings indicated distant metastases in 6 of 63 patients. Metastatic disease was confirmed in five of these six patients (8%, 95% confidence interval: 3-18%). FDG-PET scan also detected regional lymph node metastases even in nine patients (14%) in whom computed tomography images had been negative, including contralateral lymph node metastasis in three patients. FDG-PET scan detected additional lesions in patients diagnosed as having LD-SCLC by conventional staging procedures. The therapeutic strategies were changed in 8% of patients based on the results of FDG-PET. FDG-PET scan is recommended as an initial staging tool for patients with this disease.

[A case of pulmonary infection due to Mycobacterium simiae].

A 61-year-old woman presented to our hospital with a chronic cough. She had been diagnosed with pulmonary infection due to non-tuberculous mycobacteria by her previous doctor and had received antimycobacterial chemotherapy for 1 year. Chest radiography and computed tomography on the first visit to our hospital revealed nodular shadows with a cavity in the right upper lung field and infiltrative shadows with bronchiectasis in the lingular segment. Mycobacterium simiae was identified using DNA hybridization methods. Analysis of base sequences from sputum samples using 16S rRNA confirmed the identity of all tested isolates as Mycobacterium simiae, and the organism was isolated repeatedly from sputum mycobacterial tests. Pulmonary infection due to Mycobacterium simiae was diagnosed. Rifampicin, Ethambutol and Clarithromycin were administered to the patient, but clinical symptoms have continued, and findings on chest radiography have deteriorated. Cases of pulmonary infection due to Mycobacterium simiae are rare, and this represents the first such case reported in Japan.

Metachronous colon tumors: risk factors and rationale for the surveillance colonoscopy after initial polypectomy.

PURPOSE: We analyzed the possible risk factors for metachronous colon tumors after endoscopic resection of initial tumors. METHODS: Three hundred and twenty-one patients entered the surveillance study after colonoscopic resection of initial tumors between 1985 and 1999. Histology of initial tumors was adenoma in 214 patients and carcinoma in 107 patients. Solitary tumor was observed in 196 patients and multiple tumors in 125 at initial endoscopy. The median surveillance period was 39 (range, 12-112) months, and the median frequency of surveillance colonoscopy was three (range, 2-10) times. RESULTS: Metachronous neoplasms were identified in 114 of 321 surveillance cases (36%). In the 114 cases, the number of patients with metachronous adenoma was 103 (90%) and that of carcinoma was 11 (10%). Clinical characteristics at entry - including age, gender, multiplicity of polyp, histology of polyp, and site of polyp - were not different between patients with metachronous tumors and those without metachronous tumors. Kaplan-Meier analysis revealed that patients with a histology of carcinoma and those with multiple polyps at entry developed metachronous tumors significantly earlier than did patients with initial adenomas and initial solitary polyp, respectively ( P<0.001, P<0.001). However, other characteristics at entry did not produce significant differences in the rate of the development of metachronous tumors using Kaplan-Meier analysis. Proportional hazards model analysis revealed that histology of the initial tumor as carcinoma (relative risk, 1.690, 95% confidence interval, 1.118-2.555) and multiplicity (1.472, 1011-2.143) were significant risk factors for metachronous colon tumors. The 75%, 50%, and 25% metachronous tumor-free periods after initial polypectomy were 14, 21, and 39 months, respectively. CONCLUSIONS: These results may help optimizing surveillance strategies for metachronous colon tumors and raising the economic benefit of colonoscopy.